Table 1 Effect of Internalization on the Affinity of Commonly Used Neuroimaging Agents

From: Impact of D2 Receptor Internalization on Binding Affinity of Neuroimaging Radiotracers

Type of ligand

Pharmacology

Ligand (number of experiments)

Surface D2 receptor (Q−/MTSET−) (Ki (s) , nM)

Internalized D2 receptor (Q+/MTSET+) (Ki (i) , nM)

Affinity shift (Ki(i)/Ki(s))

Lipophilicity (Log P† or Log kw‡)

Imaging

Antagonist

Raclopride (6)

0.50±0.08

1.00±0.35*

2.1

1.3† (Laruelle, 2000)

  

FLB 457 (5)

0.03±0.01

0.09±0.02**

3.0

1.9‡ (Loc'h et al, 1996)

  

Epidepride (6)

0.01±0.01

0.03±0.01*

2.4

2.1‡ (Kessler et al, 1991)

  

Fallypride (6)

0.32±0.06

0.92±0.31**

2.9

2.4† (Laruelle, 2000)

  

IBZM (9)

0.19±0.05

0.23±0.11

1.2

2.8† (Laruelle, 2000)

  

NMSP (6)

0.07±0.01

0.13±0.02**

1.9

3.3† (Laruelle, 2000)

 

Agonist

PHNO (9)

2.62±0.56

5.67±2.90*

2.2

2.1† (Wilson et al, 2005)

  

NPA (6)

0.97±0.28

1.02±0.33

1.1

2.5† (Wilson et al, 2005)

Control

Agonist

Dopamine (6)

870.3±146

19,337±4265**

22.2,

0.6a,†

  

Quinpirole (7)

900.4±138.3

856.1±120.5

1.0

2.4a,†

 

Antagonist

Sulpiride (3)

10.3±2.3

202,000±25,300**

19,600

1.3† (de Paulis et al, 1988)

  1. aCalculated with Chemdraw Ultra 11.0.1 (CambridgeSoft, Cambridge, MA).
  2. *p<0.01 vs Ki(s); **p<0.001 vs Ki(s), t-test.
  3. Ki values were measured for surface (Ki(s), Q–/MTSET– conditions) and internalized (Ki(i) Q+/MTSET+ conditions) D2 receptors.
  4. Two-way ANOVA restricted to the imaging agents with conditions (Q−/MTSET− vs Q+/MTSET+) and ligands as factors further revealed a significant effect of conditions (p=0.003), ligands (p<0.001), and condition by ligand interactions (p<0.001).
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